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Apigenin (APG), a bioactive flavonoid with promising therapeutic potential, suffers from poor water solubility, which limits its bioavailability. To address this, solid dispersions of APG were prepared using ball milling with sodium alginate (SA), Pluronic® F-68 (PLU68), Pluronic® F-127 (PLU127), PVP K30, and PVP VA64 as polymeric excipients. These dispersions were screened for apparent solubility in water and buffers with pH 1.2, 5.5, and 6.8. Based on improved solubility after 60 min, APG–PLU68 and APG–PLU127 dispersions were selected for further study. DSC and FT-IR analysis confirmed molecular interactions between APG and the polymer matrices, contributing to enhanced solubility and dissolution rates. Dissolution rate studies showed that APG–PLU127 achieved 100% solubility at pH 6.8, suggesting its potential use in environments such as the small intestine. Additionally, APG–PLU127 exhibited 84.3% solubility at pH 1.2, indicating potential for solid oral dosage forms, where APG could be absorbed in the acidic conditions of the stomach. The stability study confirmed that storage for one year under ambient conditions does not cause chemical degradation but affects the physical state and solubility of the dispersion. Antioxidant activity was assessed using the ABTS assay. Freshly obtained APG–PLU127 showed 68.1% ± 1.94% activity, whereas APG–PLU127 stored for one year under ambient conditions exhibited 66.2% ± 1.62% (significant difference, p < 0.05). The difference was related to a slight decrease in the solubility of APG in the solid dispersion (T0 = 252 ± 1 μg∙mL−1, T1 = 246 ± 1 μg∙mL−1). The findings demonstrate the superior performance of PLU127 as a carrier for enhancing the solubility, release, and antioxidant activity of APG. [ABSTRACT FROM AUTHOR]

The influence of ionizing radiation on the physicochemical properties of panipenem in the solid-state was studied. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile panipenem. Spectroscopic (FT-IR, Raman), chromatography (HPLC and HPLC-MS) and X-ray powder diffraction (XRPD) studies have shown that irradiation of panipenem with the 25 kGy, the dose required to achieve sterility, does not change the physicochemical properties of the studied compound. The antimicrobial activity of panipenem irradiated with the dose of 25 kGy was reduced for three species. It was confirmed that the decrease in antimicrobial activity might be related to the isomerization of panipenem. [ABSTRACT FROM AUTHOR]

This study aimed to investigate changes in the solubility and antimicrobial efficacy of cefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated in silico model was used. A theoretical model based on docking and molecular mechanics/generalized born surface area was validated using a curated dataset of API (active pharmaceutical ingredient)-CD stability constants. The library of commonly used cyclodextrins was virtually screened, indicating CA -hydroxypropyl-βCD (HPβCD) as the most thermodynamically favored system. Solid-state CA-HPβCD system was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles of the CA and its cyclodextrin system were evaluated. Microbiological activity of the CA-HPβCD inclusion system was studied based on changes in minimal inhibitory concentration (MIC) values and related to ones of the pure CA. The theoretical model was successfully validated, obtaining an average correlation with experimental data R = 0.7. The dissolution study showed significantly improved dissolution profiles of CA-HPβCD compared to CA. HPβCD increases the antimicrobial efficacy of CA up to 4-fold compared to pure CA. [ABSTRACT FROM AUTHOR]

Paracetamol (acetaminophen), a pain-killer with antipyretic properties, shows structural polymorphism. It occurs in three polymorphic forms: monoclinic, orthorhombic, and unstable form III. In the study, the commercially available samples of paracetamol (P1 and P2) were examined using X-ray powder diffraction, infrared, and Raman spectroscopy. Results demonstrated that all of the methods defined polymorphic forms of paracetamol in the samples. However, only Raman spectroscopy and PXRD methods detected impurities in the sample P1. These methods transpired to be more sensitive than the FT-IR method, which identified samples of paracetamol as one structural form (monoclinic polymorph). Moreover, the Raman spectroscopy identified impurities in the form P1 as changes in the crystalline form. [ABSTRACT FROM AUTHOR]

Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-β-cyclodextrin (tedizolid/HP-β-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives. [ABSTRACT FROM AUTHOR]

Synthesis and structural characterization of new esters of oleanolic acid and its 11-oxo derivatives are reported. Compounds crystallize in four isostructural groups, each containing one to four structures. Single-crystal X-ray analysis revealed that molecules belonging to non-isostructural groups self-associate according to two schemes that describe also supramolecular architectures in crystals of glycyrrhetinic acid derivatives. Structural motifs arise as a result of van der Waals forces. Parameters introduced for the analysis of one- and two-dimensional assemblies allow the comparison of motifs in isostructural and non-isostructural crystals, including polymorphs, and a qualitative assessment of differences in molecular self-assembly. One-, two- or three-dimensional similarity has been confirmed by XPac calculations.

Due to the destruction of the integrity of the parent crystal, single-crystal-to-single-crystal phase transition in organic compounds is still a relatively rare phenomenon. The phase transition in glycyrrhetinic acid isopropyl ester is triggered by temperature change. The increasing volume of the isopropyl substituent as a result of increasing temperature forces a remodelling of the structural motifs. These changes cause a single-crystal-to-single-crystal phase transition. The low-temperature form is isostructural with glycyrrhetinic acid methanol solvate, while the high-temperature phase is isostructural with the ethyl ester of this acid.

The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds.

Carbenoxolone (CBXH2), a pharmaceutically relevant derivative of glycyrrhetinic acid, was studied by X-ray crystallography. The crystal structures of its unsolvated form, propionic acid and dimethoxyethane solvates and a solvated cocrystal of the free acid with its monobasic sodium salt CBXH2·CBXHNa·(butan-2-one)2·2H2O reveal that the recurring motif of supramolecular architecture in all crystal forms is a one-dimensional ribbon with closely packed triterpene fragments. It does not result from strong specific interactions but solely from van der Waals interactions. The ribbons are further arranged into diverse layer-type aggregates with a hydrophobic interior (triterpene skeletons) and hydrophilic surfaces covered with carboxylic/carboxylate groups. Solvent molecules included at the interface between the layers influence hydrogen-bonding interactions between the carbenoxolone molecules and organization of the ribbons within the layer. Comparison of crystal structures of carbenoxolone, glycyrrhizic acid and its aglycone-glycyrrhetinic acid have shown the impact of the size and hydrophilic character of the substituent at the triterpene C3 atom on the supramolecular architecture of these three closely related molecules.